rs61741470

Variant names:

• chr19-36103013-T-G
• rs61741470
• NM_001083961.2:c.3401T>G

Your query was ambiguous. Multiple possible variants found:

• chr19-36103013-T-G
• chr19-36103013-T-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001083961.2(WDR62):​c.3401T>G​(p.Met1134Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0386 in 1,614,088 control chromosomes in the GnomAD database, including 1,543 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.036 (140 hom., cov: 33)
  • Exomes 𝑓: 0.039 (1403 hom.)
• Consequence: WDR62 NM_001083961.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:11
• Conservation: PhyloP100: -1.51
• Publications: 14 publications found

Genes affected

WDR62 (HGNC:24502): (WD repeat domain 62) This gene is proposed to play a role in cerebral cortical development. Mutations in this gene have been associated with microencephaly, cortical malformations, and cognitive disability. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2011]

WDR62 Gene-Disease associations (from GenCC):

• microcephaly 2, primary, autosomal recessive, with or without cortical malformations

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Illumina, Ambry Genetics, Laboratory for Molecular Medicine, G2P, ClinGen
• autosomal recessive primary microcephaly

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0021208823).
• BP6: Variant 19-36103013-T-G is Benign according to our data. Variant chr19-36103013-T-G is described in ClinVar as Benign. ClinVar VariationId is 160285.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001083961.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR62	NM_001083961.2	MANE Select	c.3401T>G	p.Met1134Arg	missense	Exon 28 of 32	NP_001077430.1	O43379-4
	WDR62	NM_001411145.1		c.3386T>G	p.Met1129Arg	missense	Exon 28 of 32	NP_001398074.1	A0A7P0TAK3
	WDR62	NM_173636.5		c.3386T>G	p.Met1129Arg	missense	Exon 28 of 32	NP_775907.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR62	ENST00000401500.7	TSL:1 MANE Select	c.3401T>G	p.Met1134Arg	missense	Exon 28 of 32	ENSP00000384792.1	O43379-4
	WDR62	ENST00000587391.6	TSL:1	n.*3261T>G		non_coding_transcript_exon	Exon 26 of 30	ENSP00000465525.1	O43379-2
	WDR62	ENST00000587391.6	TSL:1	n.*3261T>G		3_prime_UTR	Exon 26 of 30	ENSP00000465525.1	O43379-2

Frequencies

GnomAD3 genomes AF: 0.0356 AC: 5423 AN: 152180 Hom.: 137 Cov.: 33

Gnomad AFR AF: 0.0221

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.0287

Gnomad ASJ AF: 0.0642

Gnomad EAS AF: 0.111

Gnomad SAS AF: 0.0786

Gnomad FIN AF: 0.0309

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0360

Gnomad OTH AF: 0.0425

GnomAD2 exomes AF: 0.0459 AC: 11535 AN: 251038 AF XY: 0.0478

Gnomad AFR exome AF: 0.0228

Gnomad AMR exome AF: 0.0206

Gnomad ASJ exome AF: 0.0652

Gnomad EAS exome AF: 0.122

Gnomad FIN exome AF: 0.0329

Gnomad NFE exome AF: 0.0372

Gnomad OTH exome AF: 0.0447

GnomAD4 exome AF: 0.0389 AC: 56848 AN: 1461790 Hom.: 1403 Cov.: 32 AF XY: 0.0402 AC XY: 29223 AN XY: 727190

African (AFR) AF: 0.0210 AC: 703 AN: 33480

American (AMR) AF: 0.0216 AC: 968 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0681 AC: 1779 AN: 26136

East Asian (EAS) AF: 0.104 AC: 4133 AN: 39700

South Asian (SAS) AF: 0.0729 AC: 6291 AN: 86256

European-Finnish (FIN) AF: 0.0328 AC: 1750 AN: 53322

Middle Eastern (MID) AF: 0.0463 AC: 267 AN: 5768

European-Non Finnish (NFE) AF: 0.0342 AC: 38070 AN: 1112010

Other (OTH) AF: 0.0478 AC: 2887 AN: 60396

GnomAD4 genome AF: 0.0357 AC: 5434 AN: 152298 Hom.: 140 Cov.: 33 AF XY: 0.0361 AC XY: 2686 AN XY: 74480

African (AFR) AF: 0.0221 AC: 919 AN: 41578

American (AMR) AF: 0.0287 AC: 439 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0642 AC: 223 AN: 3472

East Asian (EAS) AF: 0.112 AC: 578 AN: 5178

South Asian (SAS) AF: 0.0783 AC: 378 AN: 4830

European-Finnish (FIN) AF: 0.0309 AC: 328 AN: 10628

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0360 AC: 2449 AN: 67990

Other (OTH) AF: 0.0468 AC: 99 AN: 2114

Alfa AF: 0.0370 Hom.: 83

Bravo AF: 0.0337

TwinsUK AF: 0.0337 AC: 125

ALSPAC AF: 0.0327 AC: 126

ESP6500AA AF: 0.0254 AC: 112

ESP6500EA AF: 0.0392 AC: 337

ExAC AF: 0.0474 AC: 5758

Asia WGS AF: 0.151 AC: 523 AN: 3478

EpiCase AF: 0.0380

EpiControl AF: 0.0351

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not specified (5)
-	-	3	Microcephaly 2, primary, autosomal recessive, with or without cortical malformations (3)
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.21
DANN	Benign	0.28
DEOGEN2	Benign	0.0075	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.053	N
LIST_S2	Benign	0.25	T
MetaRNN	Benign	0.0021	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N
PhyloP100		-1.5
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.65	N
REVEL	Benign	0.022
Sift	Benign	0.053	T
Sift4G	Benign	0.59	T
Polyphen		0.024	B
Vest4		0.096
MPC		0.35
ClinPred		0.0022	T
GERP RS		-5.3
Varity_R		0.30
gMVP		0.58
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs61741470; hg19: chr19-36593915; COSMIC: COSV54331568;